title: Amplification of the PDGFRA, KIT and KDR genes in glioblastoma: a population-based study.
abstract: The aim of this study was to establish the frequency of amplification of tyrosine kinase receptor genes PDGFRA, KIT and KDR (VEGFR2) at 4q12 in glioblastomas at a population level, and to assess whether such alterations have any clinical impact. Screening of 390 glioblastomas from a population-based study by differential PCR revealed amplification of the PDGFRA, KIT and KDR genes in 33 (8.5%), 17 (4.4%) and 13 (3.3%) glioblastomas, respectively. None of these alterations was prognostic for overall survival. Patients with glioblastoma showing KIT amplification were significantly younger than those with glioblastoma showing no amplification (51.7 ± 21.7 years vs. 59.3 ± 13.1 years; P=0.0231). Twelve glioblastomas showed concurrent amplification of the PDGFRA, KIT and KDR genes, whereas 18 glioblastomas showed PDGFRA amplification only. A significant inverse association was observed between KIT amplification and EGFR amplification (P=0.0260), whereas a borderline positive association was found between KIT amplification and TP53 mutation (P=0.0579). No significant difference was observed in the frequency of amplification of these genes in primary and secondary glioblastomas or in glioblastomas with and without IDH1 mutations, suggesting that amplification of PDGFRA, KIT and KDR may be implicated in the pathogenesis of a small fraction of both subtypes of glioblastoma.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Sumihito
authors.initials: S
authors.lastname: Nobusawa
authors.forename: Robert
authors.initials: R
authors.lastname: Stawski
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakazato
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ohgaki
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D040301:Vascular Endothelial Growth Factor Receptor-2